Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 404333, Taiwan.
Research Center for Cancer Biology, China Medical University, Taichung, 404333, Taiwan.
Sci Rep. 2023 Feb 16;13(1):2800. doi: 10.1038/s41598-023-30065-5.
Acinetobacter baumannii is a nosocomial pathogen that can be resistant to antibiotics by rapidly modulating its anti-drug mechanisms. The multidrug-resistant A. baumannii has been considered one of the most threatening pathogens to our society. Biofilm formation and persistent cells within the biofilm matrix are recognized as intractable problems, especially in hospital-acquired infections. Poly-β-1,6-N-acetyl-glucosamine (PNAG) is one of the important building blocks in A. baumannii's biofilm. Here, we discover a protein phosphoryl-regulation on PNAG deacetylase, AbPgaB1, in which residue Ser411 was phosphorylated. The phosphoryl-regulation on AbPgaB1 modulates the product turnover rate in which deacetylated PNAG is produced and reflected in biofilm production. We further uncovered the PgaB deficient A. baumannii strain shows the lowest level of biofilm production but has a high minimal inhibition concentration to antibiotic colistin and tetracycline. Based on bactericidal post-antibiotic effects and time-dependent killing assays with antibacterial drugs, we claim that the PgaB-deficient A. baumannii converts to colistin-tolerant cells. This study utilizes a biofilm-independent colistin-tolerant model of A. baumannii to further investigate its characteristics and mechanisms to better understand clinical outcomes.
鲍曼不动杆菌是一种医院病原体，它可以通过快速调节其抗药性机制来产生抗药性。多药耐药的鲍曼不动杆菌已被认为是对我们社会最具威胁的病原体之一。生物膜形成和生物膜基质内的持久细胞被认为是难以解决的问题，尤其是在医院获得性感染中。聚-β-1,6-N-乙酰葡糖胺（PNAG）是鲍曼不动杆菌生物膜的重要组成部分之一。在这里，我们发现了一种对 PNAG 脱乙酰酶 AbPgaB1 的蛋白磷酸化调节，其中残基 Ser411 被磷酸化。AbPgaB1 的磷酸化调节调节了产物转化速率，即产生脱乙酰化的 PNAG，并反映在生物膜的产生上。我们进一步发现，缺乏 PgaB 的鲍曼不动杆菌菌株表现出最低水平的生物膜产生，但对抗生素多粘菌素和四环素的最小抑制浓度很高。基于杀菌后抗生素效应和抗菌药物的时间依赖性杀伤试验，我们声称 PgaB 缺陷的鲍曼不动杆菌转化为对多粘菌素耐受的细胞。本研究利用一种生物膜独立的多粘菌素耐受模型的鲍曼不动杆菌，进一步研究其特性和机制，以更好地了解临床结果。
